The proposed research is devoted to elucidation of the mechanisms by which pulmonary alveolar macrophages, cells which constitute the first line of defense in clearance of inhaled foreign matter and vigilance against pyogenic infection, ingest particulate objects. Two main avenues are proposed. One planned direction is based on the assumption that contracile proteins, similar to actins and myosins in cardiac, skeletal and smooth muscle, provide the driving force for the ameboid motion that underlies the ingestion process. The plan is to isolate and characterize these proteins from rabbit alveolar macrophages, with particular emphasis on analyzing the factors governing polymerization of action and the regulation of myosin Mg2 ion-ATPase activity under conditions likely to obtain in the intracellular environment. Particular attention will be devoted to following up preliminary findings suggesting that a novel regulatory system involving cofactors protein(s) rather than calcium may govern contractility within the alveolar macrophage. The focus on actin polymerization is based on the hypothesis that particle ingestion requires localized assembly and disassembly of the contractile organ to form the pseudopodia which characterize engulfment. The second major plan is to pursue the well known activating effect of extracellular divalent cations on ingestion by macrophages, to determine the site of this activation. The kinetics of activation of ingestion by the ions, and the binding, movement, distribution and content of Mg ions and Ca ions in alveolar macrophages will be analyzed. Contractile proteins and divalent cations will also be studied in human polymorphonuclear leukocytes, a second line of defense in pulmonary disease. These cells will be studied because it is possible to detect impaired ingestive function in them in human disease states characterized by susceptibility to pyogenic infection and to correlate the results of our studies with the disease states.